ACS Nano: Blood Clot Scaffold Loaded with Liposome Vaccine and siRNAs Targeting PD-L1 and TIM-3 for Effective DC Activation and Cancer Immunotherapy

time:2023-03-21Hits:10设置

Title:

Blood Clot Scaffold Loaded with Liposome Vaccine and siRNAs Targeting PD-L1 and TIM-3 for Effective DC Activation and Cancer Immunotherapy

Authors:

Yitong Chen1, Yue Zhang1, Beilei Wang1, Qin Fan2, Qianyu Yang1, Jialu Xu1, Huaxing Dai1, Fang Xu1, and Chao Wang1*

Institutions:

1Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, P. R. China.

2Key Laboratory for Organic Electronics & Information Displays (KLOEID), Institute of Advanced Materials (IAM) and School of Materials Science and Engineering, Nanjing University of Posts & Telecommunications, Nanjing210023, P. R. China China.

Abstract:

Tumor vaccines have been showing a relatively weak response rate in cancer patients, while deficiencies in delivery efficiency to dendritic cells (DCs), as well as DC-intrinsic immunosuppressive signals, contribute to a great extent. In this work, we report an implantable blood clot loaded with liposomes-protamine-hyaluronic acid nanoparticles (LPH NPs) containing vaccine (LPH-vaccine) and LPH NPs containing siRNA (LPH-siRNA) for synergistic DC recruitment and activation. The subcutaneously implanted blood clot scaffold can recruit abundant immune cells, particularly DCs, to form a DC-rich environment in vivo. Within the scaffold, LPH-vaccine effectively delivers antigens and adjuvants to the recruited DCs and induces the maturation of DCs. More importantly, LPH-siRNA that targets programmed death-ligand 1 (PD-L1) and T cell immunoglobulin and mucin-containing molecule 3 (TIM-3) can reduce immunosuppressive signals in mature DCs and prevent the DCs from expressing a regulatory program in the scaffold. The activated DCs correlate with an improved magnitude and efficacy of T cell priming, resulting in the production of tumor antigen-specific T cells in multiple mouse models. Our strategy can also be used for patient-tailored therapy by change of tumor neoantigens, suggesting a promising strategy for cancer therapy in the clinic.

IF:

18.027

Link:

https://pubs.acs.org/doi/10.1021/acsnano.2c10797


Editor: Guo Jia


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